A pandemic of unknown cause is spreading across the northeast of the US, mysteriously within well-defined borders. Victims experience loss of speech and physical disorientation; they freeze, and then unfreeze to commit suicide: people jump from buildings, shoot or hang themselves, one feeds himself to lions in the zoo, some cut themselves with a hairpin, barbed wire, glass, or a grass mower, drive into a tree, etc. The initial assumption that it is a terrorist attack is abandoned.
Once these events start to get noticed, the protagonist, science teacher Elliot Moore (Mark Wahlberg), his estranged wife, Alma Moore (Zooey Deschanel), Elliot's best friend and colleague Julian (John Leguizamo), a math teacher, and Julian's eight-year-old daughter Jess (Ashlyn Sanchez) try to evacuate the city. They travel by train until the train stops at a small station in western Pennsylvania, and train services are discontinued.
Julian separates from the group , trying to reach his wife, who was taking a bus to Princeton. He requests Elliot and Alma take Jess along; they agree. Julian gets a ride from a family escaping. Once they arrive in Princeton, they see that the town has been affected and find people hanging on trees. The driver, who is affected by the toxin from a tear in the car's sunroof, suddenly crashes into a tree. Julian survives the crash but, also affected, he slashes his wrists with pieces from the windshield.
Meanwhile Elliot, Alma, and Jess get a ride with a couple, of which the man explains his theory that the plants attack people as a defense mechanism. At a crossing cars with fleeing people from all directions meet. A soldier, Pvt. Auster, takes charge, and advises people to proceed on foot. Elliot, Alma, and Jess are accompanied by another group of people. Later on, Auster is affected by the toxin, and proceeds to kill himself. The group that was following Auster also proceed to do the same. Elliot's group, who are now aware of the toxin, start to run and split into three groups. Elliot, Alma, Jess, and two boys stay together until the two boys are later shot and killed by a deranged man living in a house which the group tries to enter to get some food.
Elliot deduces that plants and trees produce an airborne neurotoxin when the number of people that are present is larger than a threshold, and also that this threshold is decreasing with time.[1] Finally even isolated people are affected. Elliot, Alma, and Jess can stay in a house of a woman who lives an isolated life. However, she gets suspicious of them and tells them they have to leave the next day after she wrongly accuses Elliot of stealing. After arguing with Elliot, the woman goes outside and gets affected by the toxin, kills herself. When they realize they have to stay inside, Elliot is in the house while Alma and Jess are in the barn. They prepare to die and have a last conversation through a speaking tube, but then go outside to meet, to die together. However, the pandemic is suddenly over, and all three survive. They adopt Jess (Julian's wife has died as well). Three months later, with Alma being pregnant, there is a new outbreak in Paris, and it is assumed that this is the full attack which will take place worldwide as was theorized on a news channel.